Phosphodiester cleavage of ribonucleoside monophosphates and polyribonucleotides by homo- and heterodinuclear metal complexes of a cyclohexane-based polyamino-polyol ligand

The ability of the dinuclear complexes of tdci [1,3,5-trideoxy-1,3,5-tris (dimethyl amino) -cis-inositol] to promote the cleavage of the phosphodiester bonds of nucleoside 2',3'-cyclic monophosphates, dinucleoside monophosphates and polyribonucleotides has been studied. The homodinuclear copper(II) and zinc(II) complexes efficiently promote the hydrolysis of cyclic nucleotides. The second-order rate constant (k(2) approximate to 0.44 m(-1)s(-1)) estimated for the cleavage of 2',3'-cAMP induced by dinuclear copper(II) complexes is about 107 times greater than that for the hydroxide-ion-catalysed reaction. The complex selectively cleaves the TO-P bond of 2',3'-cUMP and forms the 3'-product in 91% yield. An equimolar mixture of copper(II), zinc(II) and tdci proved to be more efficient than either of the binary systems: a 7-20-fold rate enhancement was observed for the cleavage of 2',3'-cNMP substrates. The half-life for the hydrolysis of 2',3'-cAMP decreased from 300 days to five minutes at 25degreesC when the concentration of each of the three components was 2.5 mm. In contrast to the copper(II) or zinc(II) complexes of tdci, the heterodinuclear species promoted the hydrolysis of several dinucleoside monophosphates. For two ApA isomers, cleavage of the 3',5'-bond was about 6.5 times faster than cleavage of the 2',5'-bond. On the basis of the kinetic data, a trifunctional mechanism is suggested for the heterodinuclear-complex-promoted cleavage of the phosphodiester bond. Double Lewis acid activation occurs when the metal ions bind to the phosphate oxygen atoms. In particular, a metal-bound hydroxide ion serves as a general base or a nucleophilic catalyst, and, presumably, a zinc(II)-bound aqua ligand behaves as a general acid and facilitates the departure of the leaving alkoxide group. The effect of the complexes on the hydrolysis of poly(U), poly(A) and type III native RNA was also investigated, and, for the first time, kinetic data on the cleavage of the phosphodiester bonds of polyribonucleotides by a dinuclear complex was obtained.